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PubMed · 856963

Glutaric aciduria: biochemical and morphologic considerations.

S I Goodman·M D Norenberg·R H Shikes·D J Breslich·P G Moe
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Abstract

Biochemical and morphologic studies on a patient with glutaric aciduria are presented. Generalized aminoaciduria, alpha-aminoadipic aciduria, and saccharopinuria were noted just prior to death, as well as glutaconic aciduria greater than beta-hydroxyglutaric aciduria. Mutant liver mitochondria did not oxidize glutaryl-CoA to glutaconyl-CoA, indicating deficiency of glytaryl-CoA dehydrogenase. Autopsy revealed cerebral edema, ischemic neuronal changes, and striatal degeneration in the brain with fatty changes in liver, kidney, and myocardium.

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Amino Acid Metabolism, Inborn ErrorsAutopsyBrainBrain ChemistryChildGlutaratesHumansHydroxylysineInfantKidneyLiverLysineMaleMitochondria, LiverMyocardiumOxidoreductasesTryptophanJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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S I Goodman, M D Norenberg, R H Shikes, D J Breslich, P G Moe. 1977. Glutaric aciduria: biochemical and morphologic considerations.. https://doi.org/10.1016/s0022-3476(77)81240-7

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Glutaric acidemia type I (GA I) (GA I, McKusick 23167; OMIM # 231670) is an autosomal recessive metabolic disorder caused by glutaryl-CoA dehydrogenase deficiency (EC 1.3.99.7). Clinically, the disease is characterized by macrocephaly, hypotonia, dystonia and diskinesia. Since the pathophysiology of this disorder is not yet well established, in the present investigation we determined a number of energy metabolism parameters, namely (14)CO(2) production, the activities of the respiratory chain complexes I-IV and of creatine kinase, in tissues of rats chronically exposed to glutaric acid (GA). High tissue GA concentrations (0.6 mM in the brain, 4 mM in skeletal muscle and 6 mM in plasma) were induced by three daily subcutaneous injections of saline-buffered GA (5 micromol x g(-1) body weight) to Wistar rats from the 5th to the 21st day of life. The parameters were assessed 12 h after the last GA injection in cerebral cortex and middle brain, as well as in skeletal muscle homogenates of GA-treated rats. GA administration significantly inhibited the activities of the respiratory chain complexes I-III and II and induced a significant increase of complex IV activity in skeletal muscle of rats. Furthermore, creatine kinase activity was also inhibited by GA treatment in skeletal muscle. In contrast, these measurements were not altered by GA administration in the brain structures studied. Taken together, it was demonstrated that chronic GA administration induced an impairment of energy metabolism in rat skeletal muscle probably due to a higher tissue concentration of this organic acid that may be possibly associated to the muscle weakness occurring in glutaric acidemic patients.

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